AbstractA library of polyhydroxylated pyrrolidines was obtained by performing a tandem Staudinger/aza‐Wittig/Ugi three‐component reaction on a L‐ribose‐derived 4‐azido aldehyde. In this paper we describe the effect of Lewis acids on the diastereoselectivity of the final Ugi three‐component reaction step that the intermediate (D‐lyxo‐pyrroline) cyclic imine undergoes. When the Ugi reaction was performed in methanol almost exclusively pyrrolidines with a 2,3‐cis relationship were formed. However, a significant amount of 2,3‐trans product was formed upon addition of Lewis acids to the Ugi reaction mixture. The scope of this effect is explored by evaluating a diverse set of Lewis acids in combination with variation of other reaction parameters and the carboxylic acid/isocyanide component. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)